1. Field of the Invention
The present invention relates to a method of inhibiting the metabolism of cholesterol, and the use of dioxabicyclo [33.0] octane derivative for producing a pharmaceutical preparation to be used for inhibiting the metabolism of cholesterol.
2. Description of the Related Art
Cholesterol is the main sterol of higher animals, present in all the tissues, an important component of the cell wall, and is used in vivo in a large amount as a starting material of the bile acids. Cholesterol is synthesized in the liver and other organs, and further intaken from the food. However, it is epidemiologically believed that a large amount of intake of saturated fatty acids or cholesterol provides a relatively high concentration of serum cholesterol and a high mortality due to coronary heart diseases. Therefore, to treat diseases caused by hypercholesteremia, cholesterol intake inhibitors, accelerators of disassimilatory excretion of cholesterol to the bile acids, or cholesterol biosynthesis inhibitors are used. On the other hand, it is epidemiologically recognized that there is a positive correlations between the amount of fat intake and a mortality from colon cancer. Namely, according to epidemiological research, the morbidity rate of colon cancers is found to positively correlate with an amount of intake of fat and protein (Wynder Cancer Res., 35,33 88, 1975). An increase of the intake of animal fat is related to an increase of cholesterol, and a role of metabolites thereof by enteric bacteria in the oncogenesis is noted. It is known that cholesterol is metabolized to neutral steroids such as coprostanol, coprostanone, cholestanol and the like, and in the area having a high risk of colonic cancers, a concentration of neutral steroids in the feces is high. Moreover, it is reported that cholesterol dehydrogenase, which is known as an enzyme converting cholesterol to coprostanol, is present at a high level in patients suffering from colon cancer.
Moreover, an amount of animal fat highly correlates with mortality due to breast cancer, and this phenomenon is explained in that a high animal fat food increases the amount of excretion of the bile acids and cholesterol into the bile, and they are metabolized by enteric bacteria to estrogen, which then promotes oncogenesis of breast cancer.
Nevertheless, currently, there are no known substances which inhibit the metabolism of primary bile acids and cholesterol.
Accordingly, a new method of inhibiting the metabolism of cholesterol is urgently sought.